Study Detects Risk of Cancer Due to Unexpected Weight Loss in Adults

Researchers indicated the risk for those presenting to primary care physicians is 2% or less and does not warrant further investigation under current UK guidelines.

According to a study published in The BMJ, the risk of cancer in adults with unexpected weight loss presenting to primary care is 2% or less, and therefore does not warrant further investigation under current UK guidelines.1

However, the researchers suggested that in male ever smokers who are 50 years of age or older and in patients with concurrent clinical features, the risk of cancer merits the recommendation of invasive investigation.

“[General practitioners] face a dilemma when faced with a patient who may have cancer but whose symptoms are not enough to justify further investigation immediately and which don’t point to a specific type of cancer,” Paul Aveyard, FRCGP, FFPH, practicing general practitioner and professor of Behavioural Medicine at the University of Oxford, said in a press release.2 “This study lets us define some key signs and symptoms to help [general practitioners] home in on the right course of action much quicker – which should improve patient outcomes.”

Using the Clinical Practice Research Datalink electronic health records data linked to the National Cancer Registration and Analysis Service in primary care in England, researchers identified 63,973 adults with a code for unexpected weight loss from January 1, 2000 to December 31, 2012. The primary end point for the study was a cancer diagnosis in the 6 months following the earliest weight loss code.

Of the total cohort, 37,215 (58.2%) were women, 33,167 (51.8%) were aged 60 years older, and 16,793 (26.3%) were ever smokers. Moreover, 908 (1.4%) had a diagnosis of cancer within 6 months of the index date, 882 of which (97.1%) were aged 50 years or older.

Though the positive predictive value for cancer was above the 3% threshold recommended by the National Institute for Health and Care Excellence for urgent investigation in male ever smokers aged 50 years or older, it was not for women at any age. Overall, 10 additional clinical features were correlated with cancer in men with unexpected weight loss and 11 in women. Clinical features co-occurring with unexpected weight loss were associated with multiple cancer sites.

Positive likelihood ratios in men ranged from 1.86 (95% CI, 1.32-2.62) for non-cardiac chest pain to 6.10 (95% CI, 3.44-10.79) for abdominal mass, and in women from 1.62 (95% CI, 1.15-2.29) for back pain to 20.9 (95% CI, 10.7-40.9) for jaundice. Further, abnormal blood test results correlated with cancer included low albumin levels (4.67; 95% CI, 4.14-5.27) and raised values for platelets (4.57; 95% CI, 3.88-5.38), calcium (4.28; 95% CI, 3.05-6.02), total white cell count (3.76; 95% CI, 3.30-4.28), and C reactive protein (3.59; 95% CI, 3.31-3.89). However, no normal blood test result by itself ruled out cancer.

“We know that there is an increased likelihood of a cancer diagnosis within 6 months of seeing a [general practitioner] for unexpected weight loss, so it is very important that we identify which patients should be prioritized for cancer investigation" lead author Brian Nicholson, BSc, MBChB, MRCGP, MSc, DPhil, a practicing general practitioner and clinical lecturer at the University of Oxford, said in the release. “However, there are many non-cancer reasons someone might unexpectedly find their weight dropping, such as recent lifestyle choices and changes, mental ill health, or socioeconomic factors. So, it’s important we prioritize the right patients for further investigation.”

With everything considered, the researchers indicated that clinical features thought to be specific to an individual cancer site are markers of several different types of cancer when they co-occur with unexpected weight loss, which ultimately support new, broader investigative approaches for this patient population.


1. Nicholson BD, Aveyard P, Price SJ, Hobbs FDR, Koshiaris C, Hamilton W. Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study. The BMJ. doi: 10.1136/bmj.m2651

2. Prioritising patients with unexpected weight loss for cancer investigation [news release]. University of Exeter. Published August 13, 2020. Accessed September 3, 2020.

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